n  report  n

Contemporary Management Strategies

for Fibromyalgia

O
n March 21, 2009, The American Journal of Managed Care
(AJMC) held a roundtable of clinical, patient advocacy,
and managed care experts to explore issues in the diagnosis
and management of fibromyalgia. The attendees reached a consensus
on the following issues:
1. The prevalence, patient burden, and economic burden associated
with fibromyalgia merit earlier diagnosis and treatment, additional
education for the medical community (particularly primary care
physicians), and appropriate management by health plans, includ-
ing patient access to US Food and Drug Administration (FDA)-
approved fibromyalgia medications.
2. Physicians, payers, and patient advocates should work to satisfy 3
critical outcome domains for fibromyalgia patients: clinical—de-
creased symptoms and improved physical function; economic—lower
fibromyalgia-related healthcare costs; and quality of life—continued
involvement in employment, family, and social activities.
Abstract
A roundtable meeting that comprised clinical,
patient advocacy, and managed care experts
discussed issues regarding the diagnosis and
management of fibromyalgia. The panel
agreed that earlier diagnosis and treatment,
additional education for the medical community,
and appropriate management by health plans,
including patient access to US Food and Drug
Administration–approved fibromyalgia medi-
cations, are needed. In addition, physicians,
payers, and patient advocates must work to
improve clinical, economic, and quality-of-life
outcomes for fibromyalgia patients. Finally,
treatment and diagnostic guidelines must be
updated as advances in disease management
are made (including approvals of 3 new
pharmacologic agents), and development of
a therapeutic category for “fibromyalgia” on
payer formularies is needed.

3. T
 he current treatment and diagnostic guidelines for fibromyalgia (Am J Manag Care. 2009;15:S197-S218)
attempted to identify treatment options for an often misunderstood
disease state, but are not commonly used by physicians or payers as
a treatment algorithm. The guidelines have limited utility to phy-
© Managed Care &
sicians and payers because they precede or do not consider recent
Healthcare Communications, LLC
FDA approvals of 3 pharmacologic agents for fibromyalgia; their
recommendations for other treatments used for fibromyalgia are
based on data mainly from uncontrolled, small, open-label trials of
short duration; they lack a straightforward treatment algorithm (al-
though an algorithm might be problematic given the idiosyncratic
nature of the disease); and they need to be updated as advances in
disease management are made.

4. The development of a therapeutic category for “fibromyalgia” on

payer formularies would benefit patients, physicians, and pay-
ers as a step toward further legitimizing the disease state, raising
awareness of fibromyalgia, educating physicians and patients on
available FDA-approved treatments, enhancing patient access
through improved and appropriate recognition of FDA-approved
treatments, and improving understanding of disease-specific drug
utilization by payers. For participant information and disclosures, see end of text.

VOL. 15, No. 7 n  The American Journal of Managed Care  n S197

Reports

SECTION 1. FIBROMYALGIA: CLINICAL paresthesias, irritable bowel or bladder symptoms,

OVERVIEW AND ECONOMIC BURDEN anxiety, temporomandibular joint pain, restless legs,
Fibromyalgia (FM) is a multisymptom condition and/or hypersensitivity to noise, heat, and cold.1-7,13
characterized by chronic widespread pain (CWP) Comorbidities, which are far more common in FM
and usually accompanied by a multitude of addi- patients than controls, may include other neuro-
tional symptoms.1-7 Most people with FM suffer from pathic or gastrointestinal (GI) disorders, migraine,
decreased physical function,2,3,8-10 which can lead to respiratory or circulatory conditions, and mental and
disability.6,11,12 Sleep disturbances, fatigue, and morn- mood disorders (Figures 1A and 1B).4
ing stiffness are present in more than 73% of FM The pain of FM is distinctive. Patients with FM
patients.1 Many patients have headaches, cognitive have CWP for 3 months or longer in all 4 quad-
impairment, decreased well-being, depressed mood, rants of the body, but not centered in the joints, as

n  Figure 1A. Patient-Reported Symptoms at Diagnosis of Fibromyalgia

10
10 9

8 7 7

6
Patients, %

6 5 5
4 4 4
4 3
2
2

0
ue es s s d ps s r
lar ee
p ain ch leg es ire
d
ire n es ajo
cu ain tig Sl ities tp bn pa ory am sn M ion
us Fa in da ss cr pa tio ou
p al o a
stl
e m Im em Im tra ss
M
rm
J He Nu Le
g
n r v
pr
e
no Re m ce Ne de
ab con

Adapted from Kranzler JD, et al. Psychopharmacol Bull. 2002;36(1):165-213.

Figure 1A
n  Figure 1B. Comorbidities Associated With Fibromyalgia

Fibromyalgia (n = 33,176) Controls (n = 33,176)

Painful neuropathic disorders

Musculoskeletal diseases
Digestive diseases
Respiratory diseases
Circulatory diseases
Migraine
Depression
Diabetes
Neoplasms

0 5 10 15 20 25 30

Adapted from Berger A, et al. Int J Clin Pract. 2007;61(9):1498-1508.

S198   n  www.ajmc.com  n JUNE 2009


with rheumatoid arthritis.1,4,14,15 FM patients have a
lower pain threshold than healthy control subjects9;
generalized tenderness includes allodynia (pain from
normally nonnoxious stimuli) and hyperalgesia (in-
creased response to painful stimuli).6,16 Although they
cannot detect pressure, electrical, or thermal stimuli
at lower levels than controls, the stimulus level that
causes pain is lower.9,14,17 This phenomenon is inde-
pendent of psychological factors such as expectancy
and hypervigilance.17 The pain of FM may even per-
sist after stimuli cease.18
FM is more widespread than many are aware (Fig-
ure 2) and is believed to be underdiagnosed and un-
dertreated. In the United States the prevalence is 2%
to 4%2,4,19-21 with onset usually at 20 to 55 years,4 but
prevalence increases with age.21 The female-to-male
ratio is up to 9:1.4,21 FM is the second most common
disorder treated by rheumatologists, after osteoarthri-
tis.20 Managed care participants in the roundtable were
surprised by the prevalence and said patients were dif-
ficult to track due to use of a broad range of diagnoses
and varied drug utilization. Since prescription claims
data do not consistently include International Classifi-
cation of Diseases (ICD-9 or -10) diagnosis information
(although the data can be included, it is not typically
n  Figure 2. Epidemiology of Fibromyalgia in the General Population
7
Percent With Fibromyalgia
6
1
0
-29 -39 -49
18 30 40
Age Group, years
Reprinted with permission from Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28.
VOL. 15, No. 7 n  The American Journal of Managed Care  n S199
Contemporary Management Strategies for Fibromyalgia
required by payers, thus not captured), pharmacy uti-
lization data cannot be used with certainty to identify
patients with FM, because many of the drugs and drug
classes prescribed are also used for a variety of other
medical conditions.
With its many and variable symptoms, some of
which can occur in other disorders, FM can be dif-
ficult to identify. Recent laboratory, positron emission
tomography,22 voxel-based morphometry,23 and func-
tional magnetic resonance imaging (fMRI) research
has supported the legitimacy of FM as a genuine dis-
order.6,7,20 Nevertheless, legitimacy as a discrete entity
is still not universally accepted,5,20,24,25 which can re-
sult in problems for patients afflicted with FM, from
stigma to difficulty obtaining accurate diagnosis and
treatment.
Dr. Goldenberg (Rheumatology): I discuss this as
a problem with pain volume control, that there is a
decrease in threshold to various noxious stimuli. It’s
not just pain. It’s all stimuli. So you hear these weird
symptoms from people that smells, sounds, or bright
lights bother them. If they have a CNS hypersensitivity
or hyperirritability, it makes perfect sense.
Females
Males
-59 -69 -79 80
+
50 60 70
Reports

The predominant theory of pathogenesis in
FM is central sensitization due to dysregulation
of pain pathways.10,12,18 Brain imaging has demon-
strated this altered pain processing, with FM pa-
tients reporting pain at half the pressure required
to register pain in controls.7,14,20 At the different
pressures required to report similar pain, fMRI
showed the same brain areas were involved in
pain processing, indicating the FM patients and
controls experienced the pain similarly while the
stimuli were different.7 Although the exact etiol-
ogy is unknown,3,5 genetics appears to play a major
role in susceptibility.9 First-degree relatives of FM
patients have 8 times the risk for FM as the gener-
al population.9 FM has been associated with poly-
morphisms in the serotonin transporter gene and
the catecholamine-O-methyltransferase enzyme
that inactivates catecholamines.9,20 These poly-
morphisms affect the metabolism or transport of
the monoamine neurotransmitters serotonin and
norepinephrine.9 Compared with controls, FM pa-
tients have been found to have lower levels of me-
tabolites of serotonin and norepinephrine in their
cerebrospinal fluid.7,9 Serotonin and norepineph-
rine are antinociceptive9; that is, they decrease
the sensitivity of pain processing systems through
the descending central nervous system (CNS)
pain pathways.7,9 Low levels indicate dysregula-
tion of pain impulses through decreased activity in
descending antinociceptive pathways, resulting in
hyperalgesia and allodynia.7,9 The low levels of se-
rotonin and norepinephrine metabolites prevalent
in FM subjects9 suggest that serotonin and nor-
epinephrine reuptake inhibitors (SNRIs) might
help realign altered pain processing in descending
CNS pain pathways. Whereas SNRIs have had
analgesic effects in animal models of hyperalgesia
and allodynia, selective serotonin reuptake in-
hibitors (SSRIs) have not, which highlights the
particular importance of norepinephrine in pain
modulation.19 On the other hand, FM subjects are
reported to have increased levels of pronocicep-
tive transmitters substance P and glutamate that
amplify pain impulses in the ascending pain path-
way.7,9 Drugs such as anticonvulsants are thought
to function by reducing the release of pronocicep-
tive transmitters in the ascending pathway.
FM Causes Functional Impairment
FM is associated with functional disability.
The chronic, impairing symptoms of FM can
lead to loss of function, which negatively affects

n Table 1. Fibromyalgia (FM) Is Associated With Functional Disability

Employment and Productivity Other Functional Impacts Health-Related Quality of Life (HRQOL)

20%-50% of patients can work few or no
days
36% are absent from work > 2 d/mo
31% have lost employment due to FM
26%-55% receive disability or Social
Security payments
Limitations in activities of daily living are Before-treatment HRQOL scores are signifi-
as high as in rheumatoid arthritis cantly impaired compared with the general
population
Sleep impairment scores are well above HRQOL has been reported to be worse than
those in other chronic illnesses; sleep in patients with congestive heart failure,
deficits exacerbate fatigue and func- rheumatoid arthritis, osteoarthritis, perma-
tional limitation nent ostomies, chronic obstructive pulmo-
nary disease, and type 1 diabetes
Social and family activities may be
curtailed due to fatigue, pain, and/or
depression; sports and physical exercise
may become difficult or impossible
Social difficulties due to chronic pain
can lead to maladaptive illness behav-
iors (reduced activities and exercise,
involvement in disability and compensa-
tion systems), which can help perpetu-
ate functional decline

Sources: Busch A, et al. J Rheumatol. 2008;35(6):1130-1144. Bennett R, et al. Arthritis Rheum. 2005;53(4):519-527. Mease P. J Rheumatol.
2005;32(suppl 75):6-21. Dadabhoy D, Clauw DJ. Nat Clin Pract Rheumatol. 2006;2(7):364-372.

S200   n  www.ajmc.com  n JUNE 2009


work and leisure activities,26 may increase over
time, and reduces health-related quality of life
(QOL).13,25 Up to 50% of patients can work only
a limited number of days because of the disor-
der,26 and up to 55% receive disability or Social
Security payments.13,26 Participation in family
and social activities may decrease because of
fatigue, pain, and/or mood symptoms, and in-
adequate restorative sleep increases the overall
fatigue. Eventually, some FM patients become
completely disabled and incapable of continuing
employment (Table 1).
FM is also associated with a significant cost
burden on all involved, including patients and
their families, employers, and payers. The con-
dition imposes substantial direct medical costs27
and indirect costs of lost work productivity.27-29
Large US claims database analyses have dem-
onstrated these high costs.4,30,31 In a US insur-
ance database analysis of more than 60,000 FM
patients and age- and sex-matched controls, FM
patients had mean total healthcare costs ap-
proximately 3 times higher and median costs
5 times higher than controls ($9573 vs $3291
and $4247 vs $822, respectively, P <.001 for
both comparisons) (Figure 3).4 FM patients had
n  Figure 3. Healthcare Costs Are Higher Among Fibromyalgia Patients
10,000 $9573
Annualized Mean Healthcare Costs, $
7500
5000
2500
0
Fibromyalgia
Reprinted with permission from Berger A, et al. Int J Clin Pract. 2007;61:1498-1508.
• Mean annual healthcare costs were 3 times higher in fibromyalgia vs controls ($9573 vs $3291)
• Costs related to pain medications were 11% for fibromyaglia, vs 4.3% for controls
VOL. 15, No. 7 n  The American Journal of Managed Care  n S201
Contemporary Management Strategies for Fibromyalgia
4 times as many doctors’ office and emergency
department visits as control patients.4 FM pa-
tients were almost 4 times as likely to receive
pain-related prescription medications (includ-
ing antidepressants) and also significantly more
likely to receive non–pain-related medications.4
Almost half of the FM patients also had health-
care encounters for symptoms other than CWP,
including headache, abdominal pain, chest pain,
fatigue, and GI symptoms; psychiatric comorbid
diagnoses were also significantly higher than in
controls.4
Another claims database analysis of more than
15,000 privately insured US employees (FM, n =
8513; control, n = 7260) found that total annual
medical, prescription drug, and indirect costs of
FM patients were almost double those of con-
trols ($10,199 vs $5274, P <.0001).30 Total di-
rect costs (medical utilization plus prescription
drugs) were 86% higher for employees with FM
versus controls ($7286 vs $3915, P <.0001).30
Total costs for FM approached those of osteoar-
thritis ($10,199 vs $10,861, P = .3758), and in-
direct costs were significantly higher in FM than
osteoarthritis ($2913 vs $2537, P <.0001).30
Compared with osteoarthritis, FM was associ-
Inpatient care
Outpatient care
Pain-related medications
Other medications
Other medical care
$3291
Comparison Group
Reports
ated with more claims for comorbidities such as
psychiatric diagnoses, chronic fatigue syndrome,
and most pain disorders.30
A single-employer US administrative claims
database of 4699 employees with at least 1 FM
claim found significantly higher total annual
costs for FM claimants compared with typical
beneficiaries ($5945 vs $2486, P <.001).31 Medi-
cal utilization and prescription drug costs were
significantly higher in FM claimants (P <.001).31
Disability prevalence was twice as high among
employees with FM (P <.001).31 Employees with
FM who filed disability claims incurred $6669
in healthcare costs and $5654 in disability costs
for total annual costs of $14,100 per employee.31
Each dollar spent by the employer on FM-spe-
cific claims was matched by $57 to $143 spent
on other direct and indirect costs.31 The authors
concluded that the employer burden was sub-
stantially increased by hidden costs of comor-
bidities and disability.31
Dr. Fouts (Family Medicine): I think I’m the type
of person who needs to be educated. I’m
the type of doctor who needs to be on the
forefront of treating it. I would compare the
situation with FM similar to depression 10 to
15 years ago where somebody went into their
family doctor, and they just didn’t want to talk
about it. But if you did get them to talk about
it, often their doctor didn’t really want to take
care of it. I think education will help overcome
these situations.
Studies in Europe and Canada have shown
similar high direct and indirect costs associated
with FM.27,29 In addition, these types of claims
database analyses do not include the costs of
over-the-counter medications and uncovered
alternative treatments, which could bring total
costs even higher. The roundtable participants
agreed that FM imposes high costs on the US
healthcare system and speculated that the costs
in the published studies likely underestimate
reality.
Diagnosis of FM
The FM diagnosis can be difficult to diag-
nose and often is delayed. Although the leading
S202   n  www.ajmc.com  n JUNE 2009
theory of pathogenesis—central sensitization
from dysregulated pain pathways—is supported
by neurotransmitter, neurohormone, and sleep
physiology irregularities, objective biomarkers
of disease activity have not been validated.10
Because no objective laboratory test or marker
exists, diagnosis is based on history and physi-
cal examination.13 FM should be diagnosed by
its own clinical characteristics. Differential di-
agnosis is subtle, as FM can be difficult to dis-
tinguish from conditions with similar symptoms
that may or may not be present as comorbidi-
ties.1,4,13,20 The roundtable participants observed
that many patients self-diagnose FM and then
initiate discussion of the diagnosis with their
doctor. They said that physician familiarity with
the disorder has been improving in recent years,
but the current state of FM recognition among
primary care physicians (PCPs) is low and corre-
sponds to that of depression about 10 to 15 years
ago. Nevertheless, it has been documented that
PCPs are capable of diagnosing FM with similar
accuracy to specialists. A retrospective analysis
of 646 consecutive rheumatology patients at an
academic medical center in Israel found that of
the 196 patients referred with an initial diag-
nosis of FM, 71% had that diagnosis confirmed
by the consultant rheumatologist.32 The kappa
statistic demonstrated a good level of agreement
between the family practice physicians and rheu-
matologists (kappa = .70, P <.001).32 Sensitivity
of the FM diagnosis by the family physicians was
87% and specificity was 88%.32 The authors said
PCPs in the area were well-informed about FM
because of ongoing FM research at the medical
center. They speculated that the strong results
of the study may be related to this knowledge
base among the generalists.32 The Israeli study
highlights the need for additional education
about FM in the US medical community, partic-
ularly the primary care community. If FM can be
diagnosed accurately by a PCP without referral
to specialists, then the extended time and effort
commonly spent in obtaining an accurate diag-
nosis can be reduced, and an effective treatment
plan can be initiated earlier.
Diagnosis of FM entails assessment of pain
and other symptoms. In 1990 the American
College of Rheumatology (ACR) established

diagnostic criteria for FM including CWP for at
least 3 months and pain on at least 11 of 18 speci-
fied muscle tendon sites of focal tenderness (“ten-
der points”; Figure 4) on digital palpation using a
force of approximately 4 kg/cm2.1,4,7,9,17,20
Although tender points were the most pow-
erful discriminator between FM patients and
controls, tenderness is subjective and depends
on the examiner’s strength of palpation.1 ACR
diagnostic criteria are sensitive (88.4%) and
specific (81.1%) and can distinguish FM pain
from other rheumatologic conditions,1 but were
originally intended as a research tool. The cutoff
of 11/18 tender points is considered by many to
be somewhat arbitrary. Tender points may be as-
sociated with distress rather than pressure pain
threshold,9,17 and some patients have fewer than
11 tender points but still have FM.15,33 Women
are 11 times more likely than men to exceed 11
tender points on physical examination.9
Other domains besides pain must be assessed
for an accurate FM diagnosis. Some authors have
suggested the use of a structured interview with
questions about generalized fatigue, headache,
n  Figure 4. Illustration of Tender Points for Diagnosis of Fibromyalgia
Adapted from Wolfe F, et al. Arthritis Rheum. 1990;33(2):160-172
VOL. 15, No. 7 n  The American Journal of Managed Care  n S203
Contemporary Management Strategies for Fibromyalgia
sleep disturbance, neuropsychiatric complaints,
numbness or tingling, and irritable bowel symp-
toms.7,34 More recently, expert panels have recom-
mended additional core domains of FM for study
investigation, including multidimensional func-
tion, cognitive dysfunction, and health-related
QOL.10 A need exists, especially in the primary
care community, for better diagnostic criteria and
objective tools to assess illness severity.
Delays in Diagnosis
It is possible that difficulty in diagnosing FM may
have contributed to its underrecognition and under-
diagnosis. Diagnosis and treatment can be delayed
for years with many healthcare visits, referrals, diag-
nostic tests, a variety of diagnoses, and little impact
on symptoms.4,5,28 Roundtable participants noted that
according to the American Pain Foundation (APF),
chronic pain disorders including FM take 2 to 3 years
and 8 to 13 healthcare professionals to be diagnosed
accurately. Diagnostic delay may result from physi-
cian skepticism of the disease state, despite objective
evidence and recognition of FM by key organizations
including the ACR, Social Security Administration,
Reports

and World Health Organization.1,35 Some physicians
still believe FM is a manifestation of another un-
derlying disorder,5,25 and others question the ACR
criteria and therefore the validity of the diagnosis.6
Roundtable participants stated that diagnostic delay
may also result from lack of confidence on the part
of PCPs due to the need for an objective diagnos-
tic test or confusion about the role of tender points.
Regardless of the reason, participants acknowledged
that delayed diagnosis increases costs for insurance
companies while adding to burden on patients.
The impact of a delayed diagnosis of FM is great-
est on the patient. According to the roundtable par-
ticipants, patients with undiagnosed, untreated FM
feel frustrated and vulnerable, do not know what is
wrong with them, and may quit working. The partici-
pants agreed that delayed diagnosis adversely affects
outcomes, because the disease state is more advanced
by the time patients receive adequate management.
Years can be wasted with misdiagnosis or no diagnosis
while disease progression continues. Early diagnosis
and treatment do not occur often enough, but would
be beneficial.5,9,20 Studies have shown that symptoms
and health satisfaction improve after diagnosis of
FM.9,20 Diagnosis rules out other more serious condi-
tions, and treatment gives patients hope and a sense
of control.5 After diagnosis, patients’ well-being may
improve, in part, simply because of the recognition
about their pain and illness.5
Dr. Beltran (Managed Care): One of the biggest
challenges in healthcare management is treat-
ing chronic care illnesses like FM. It sounds
like an opportunity for a team approach. One
of the reasons there is delay in diagnosis is
that patients are referred to different spe-
cialists in different temporal time frames as
opposed to approaching the problem as a
team, where you are getting all the key spe-
cialists, whether it be the rheumatologists,
neurologists, pain management, and psychia-
try, in the same room.
Delayed diagnosis can also increase costs to pay-
ers and patients.5,28 Retrospective database analyses
revealed that earlier diagnosis of FM was associated

n  Figure 5. The Impact of a Fibromyalgia Diagnosis on Utilization of Diagnostic Testing

200
Rate Per 100 Person-Years

150

100

50

–10 –5 0 5
Years Relative to Index Date

95% Confidence interval

Case
Control

Reprinted with permission from Hughes G, et al. Arthritis Rheum. 2006;54(1):177-183.

S204   n  www.ajmc.com  n
Fig 5 JUNE 2009

with cost savings.5,28 After diagnosis of FM, medi-
cal resource utilization decreased, including visits
for comorbidities.5,28 Decreases occurred in related
testing and laboratory costs (Figure 5), medica-
tion costs, referrals, physician visits, and emergency
department visits.5,28 One author concluded that
healthcare providers might “…be legitimately con-
cerned not only with the costs of diagnosing FM
but also with the costs of not diagnosing FM.”28 The
roundtable participants speculated that the docu-
mented costs of delayed diagnosis are probably even
higher in reality, with more advanced disease feed-
ing into higher costs after later diagnosis.
Dr. Garber (Managed Care): I was truly shocked
that we had as many [fibromyalgia] cases
diagnosed as we had.… I think it would be
worthwhile for us to look into the cost of tak-
ing care of FM.
The Need for Education About FM
The roundtable participants agreed that an
understanding of the FM disease state and an ac-
curate diagnosis of FM by the medical community
still requires considerable education, especially
for PCPs. Better understanding of FM should be-
gin with more exposure to it in medical school.
Universally accepted diagnostic and treatment
algorithms do not exist, but evidence-based in-
formation is available and should be more widely
disseminated. Patient advocacy groups, health
plans, and pharmaceutical companies can help
disseminate this information, especially to PCPs
and nurse case managers, and facilitate interac-
tion of community specialists with PCPs.
Dr. Draud (Psychiatry): From a cost perspective...
people are much more expensive to treat
after they have had 2 years of disease state
progression.
The participants agreed that greater aware-
ness and understanding of FM among providers,
especially PCPs, can lead to earlier, appropriate
diagnosis and treatment. Accurate diagnosis can
reduce emergency department and office visits,
diagnostic tests, and the use of ineffective medi-
cations. Patients feel relieved after receiving an
VOL. 15, No. 7 n  The American Journal of Managed Care  n S205
Contemporary Management Strategies for Fibromyalgia
accurate diagnosis, which lifts the burden of un-
certainty about their health. They may therefore
reduce the number of drugs they continue tak-
ing. Earlier, more effective treatment can arrest
or minimize further decline of function, enabling
continued employment and greater health-related
QOL. The participants concluded that identifying
patients earlier in the disease continuum would
improve patient outcomes and help control costs.
Ms. Gleason (Patient Advocacy): So many of the
healthcare providers are uneducated about
FM as a whole. Even for medications that
have been approved by the FDA, providers
may not have a treatment regimen in mind
or know what they are going to do with the
patient.
 nother Need for Patients and Providers:
A
Treatment Access
Access to treatment for FM is sometimes re-
stricted, and is most visibly seen with respect to
utilization of specific drug therapies. The round-
table participants expressed concern that these
restrictions could impede effective treatment,
but also noted these issues are common to many
medical areas, not just FM.
Dr. Garber (Managed Care): I think there is a pau-
city of information both among our nurse care
managers and our PCPs about the general
sense of what FM is. I think that is one place
we can use some help.
As an example, some managed care plans
mandate step-edits, prior authorization, or other
programs to manage utilization of specific drugs
or drug classes. Participants with managed care
backgrounds noted that these are meant to pro-
mote either guideline-driven therapy or fiscally
responsible medication use. Often these programs
require use (and failure) of generic drug products
before authorizing branded agents. With respect
to FM, this translates to use of drugs “off-label”
before use of agents that are FDA-approved for
treatment of FM.
From the perspective of the clinicians at the
roundtable, new medications with FDA indica-
Reports
tions for FM can be difficult to obtain because
of these requirements, resulting in frustration
for both physicians and patients, after having
spent years seeking an accurate diagnosis and
treatment.
Dr. Flood (Rheumatology): It is very frustrating—
I think for everybody involved—trying to take
care of patients, and lots of confusion is gen-
erated when we are asked to use medicines
off-label for a condition. So we are sending a
lot of mixed messages, I think, through these
step-edits. I think there is a good opportunity
to rehabilitate that whole process.
Given the variability of symptoms and presen-
tation of FM among patients and the lack of clear
treatment guidelines, an optimal situation would
be to provide physicians with better flexibility
to recommend and provide the most appropriate
treatment. This consideration was tempered by
the continuing need for evidence of efficacy and
cost-effectiveness for all agents used for the treat-
ment of FM.
The roundtable participants agreed that at-
tention and appropriate management by health
plans is needed. A major challenge of managed
care is management of chronic diseases, and FM
presents opportunities for disease management
with a “center of excellence” multidisciplinary
team treatment approach. Recognizing the costs
of FM and the added costs of delayed diagnosis
and ineffective treatments, health plans can alter
policies to encourage best practices, including:
• Recognition of the diagnosis of FM
• Assistance in provider education for the di-
agnosis and treatment of FM
• Coverage of pharmacologic and nonphar-
macologic treatments that have been shown
to be effective
• Appropriate formulary placement and utili-
zation management of effective medications,
particularly drugs with FDA approval.
Summary
FM is a disorder for which early, accurate di-
agnosis and appropriate treatment are crucial to
improve clinical outcomes (ie, prevent loss of
function), reduce costs, and maintain or improve
S206   n  www.ajmc.com  n JUNE 2009
QOL. Evidence and experience suggest that im-
proved awareness and education about FM for
both patients and healthcare providers is an un-
met need. Managed care organizations can play a
role in addressing this unmet need.
Dr. Agin (Pain Specialist): When I prescribe a medi-
cation for my patient, and the patient attempts
to fill the prescription, the prescription may be
denied by their pharmacy plan outright or may
require prior authorization. A tedious process
begins. My office calls for authorization; the
pharmacy plan sends paperwork; our office
completes the paperwork and returns it. If the
patient actually fits their criteria and can get the
medication, the process can delay starting the
medications by days to weeks, or they can still
be denied after all of the paperwork is submit-
ted. If the patient is scheduled to follow up with
the prescribing physician in 2 weeks to see
how they are tolerating the medication, this
becomes an unnecessary office visit for both
the patient and the physician as the patient has
not yet had an adequate trial.
SECTION 2. CURRENT GUIDELINES FOR
THE MANAGEMENT OF FM
Despite years of clinical research and recent
FDA approvals, considerable ambiguity remains
regarding FM treatment. In addition to pharma-
cologic treatment, nonpharmacologic therapies
have been tried, including patient education, ex-
ercise, cognitive-behavioral therapy (CBT), and
alternative therapies, often in combination; and
most agree that a combination of therapies may
be the best approach.3,7,9,10,26 Many clinicians, hav-
ing received little education about FM, have scant
awareness of the demonstrated efficacy and safety
of treatment options. Each patient is unique and
the combinations of symptoms vary widely; there-
fore, treatment individualization is necessary and
a wide range of options should be readily avail-
able. However, access to some drugs is limited by
formulary restrictions, and some physicians are not
aware of the latest evidence or even recent FDA
approvals. For all of these reasons, often treatment
of FM is not evidence-based, proceeds on a trial-
and-error basis, and can continue long term with-
out sufficient efficacy. Many patients take multiple
medications for FM symptoms. Guidelines from
 Contemporary Management Strategies for Fibromyalgia

organizations such as medical specialty societies
help clinicians treat many other disorders; practi-
cal guidelines for FM would be welcome.
Several organizations have published guide-
lines for FM in this decade (Table 2). These
guidelines have offered practical guidance about
the identification and treatment of a condition
that can be difficult to identify. Moreover, the
guidelines have spurred discussion among prac-
ticing pain specialists, rheumatologists, research
investigators, and others as to the nature and
treatment of FM and what questions still need
to be answered. Establishment of guidelines in an
area such as FM is a step toward improved man-
agement by providing physicians and patients
with a channel to identify potential therapeutic
options and a base from which to develop collab-
orative treatment plans. In summary, the current
FM guidelines are a substantial early attempt to
define an often misunderstood disease state and
the treatment options for it.
However, the most recent published guidelines
for FM treatment are 2 to 4 years old, which is a
relatively long time in an environment of rapidly
changing scientific understanding. When assess-
ing the usefulness of the current guidelines, it is
necessary to balance their strengths and benefits
with some weaknesses, perhaps the most appar-
ent of which is their publication before the FDA
approvals and other important new evidence.
Current Guidelines for FM
The American Pain Society (APS) developed
evidence-based guidelines for FM diagnosis and

n Table 2. Current Fibromyalgia (FM) Guidelines

Association Objectives Methods Results

APS To provide evidence-based
(American Pain Society) guidelines for diagnosis
and management of FM
syndrome in children and
adults and to improve
quality of care
EULAR To develop evidence-based
(European League recommendations for
Against Rheumatism) the management of FM
syndrome
OMERACT OMERACT 7:
(Outcomes Measures To identify and prioritize
in Rheumatology symptom domains to be
Clinical Trials) consistently evaluated in
FM clinical trials and
identify domains and
outcomes measures for
research agenda
OMERACT 8:
To reach consensus on core
domains, evaluate outcomes
measures in recent trials,
confirm research agenda
Review of clinical trials and
meta-analyses
Rating scheme ranked evidence
Guidelines reached by consensus
of interdisciplinary panel of
13 experts
Systematic review of pharmaco­-
logic and nonpharmacologic
intervention studies
Rating scheme ranked evidence
Recommendations reached by
consensus of task force of
19 international European
experts
Delphi exercise of 23 FM
researchers established
preliminary prioritization
Patient focus groups and Delphi
exercise established patient-
identified core domains
OMERACT 7 and 8 workshop
attendees developed prioritized
list of core domains and
research agenda
Guidelines for diagnosis based
on American College of
Rheumatology criteria and other
symptomatic assessments
Guidelines for specific pharma-
cologic and nonpharmacologic
interventions
2 General recommendations for
recognition/diagnosis and
multidisciplinary approach to
management
4 Recommendations for
nonpharmacologic management
4 Recommendations for
pharmacologic management
Core domains and outcomes
measures were identified,
including patient global,
multidimensional function,
dyscognition
Composite response (patient
improvement in >2 parameters
simultaneously) recommended
as outcomes measure for
clinical trials/research agenda

Sources: Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292(19):2388-2395. Carville SF, et al. Ann Rheum
Dis. 2008;67(4):536-541. Mease PJ, et al. J Rheumatol. 2005;32(11):2270-2277. Mease P, et al. J Rheumatol. 2007;34(6):1415-1425.

VOL. 15, No. 7 n  The American Journal of Managed Care  n S207

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treatment.20,36 A consensus panel of 13 experts in
pain management disciplines performed a com-
prehensive review of 505 peer-reviewed clinical
trials and meta-analyses from the preceding 25
years.20 Guidelines were reached by expert con-
sensus and the use of a rating scheme ranking the
evidence for treatment efficacy as strong, mod-
erate, or weak.20 The clinical trials used ACR
criteria for FM and measured pain outcomes on
the Fibromyalgia Impact Questionnaire (FIQ).20
The APS guidelines recommended for diagnosis
and assessment a complete history and physi-
cal examination, including laboratory testing;
clinical diagnosis based on ACR criteria, com-
prehensive pain assessment (type, quality, loca-
tion, duration) and effect on QOL; assessment
of severity of other FM symptoms, impact on
physical/emotional function and overall QOL.36
Based on the rated evidence, the APS guidelines
recommended multiple strategies for treatment,
including both pharmacologic and nonpharma-
cologic therapies, while stressing the importance
of patient education (Table 3).20 The panel found
strong evidence for CBT, aerobic exercise, and
patient education.20 In pharmacologic therapies,
the panel found strong evidence for amitriptyline
and cyclobenzaprine, and moderate evidence to
support the use of SNRIs, SSRIs, tramadol, and
pregabalin.20
The APS guidelines have some limitations.
The evaluated studies had heterogeneous treat-
ments, short durations, and inconsistent blinding
and controls, which limits their generalizabil-
ity and practical clinical application. All of the
evaluated studies occurred before the FDA ap-
provals for FM of pregabalin, duloxetine, and
milnacipran. Most of the studies focused on pain
reduction to the exclusion of other symptoms and
outcomes including patient global improvement
and improved physical function. Finally, many of
the treatments discussed in the guidelines still
lack FDA approval for FM to date and it doesn’t

n Table 3. Comparison of APS and EULAR Guidelines for Fibromyalgia (FM) Management
Nonpharmacologic
Therapy Pharmacologic Therapy Limitations of Study Analysis

APS Strong evidence: Strong evidence: Heterogeneous treatments in studies

(American Pain Patient education Amitriptyline 25-50 mg/d Study durations generally short term
Society) CBT Cyclobenzaprine 10-30 mg/d Some studies unblinded and/or
Aerobic exercise uncontrolled
Multidisciplinary therapy Moderate evidence: Outcomes measures often exclusively
SNRIs (milnacipran, pain without assessment of
Moderate evidence: duloxetine; mixed improvements in patient global,
Strength training evidence for venlafaxine) physical function, etc
Acupuncture SSRI (fluoxetine 20-80 mg/d) All studies predated FDA approvals of
Hypnotherapy Tramadol 200-300 mg/d 3 FM pharmacotherapies
Biofeedback Anticonvulsant (pregabalin Some agents listed still lack FDA
Balneotherapy 300-450 mg/d) approval for FM

EULAR Balneotherapy (Grade B)
(European League Individually tailored
Against Rheumatism) exercise including aerobic
and strength training
(Grade C)
CBT (Grade D)
Others: relaxation, rehabilita-
tion, physiotherapy, and/or
psychological support
(Grade C)
Tramadol (Grade A) Outcome measures other than pain
Analgesics (paracetamol/ by visual analog scale and function
acetaminophen, weak by FIQ specifically excluded
opioids) (Grade D) Other limitations similar to those of
Antidepressants (amitriptyline, APS above
fluoxetine, duloxetine,
milnacipran, moclobemide,
pirlindole) (Grade A)
Tropisetron, pramipexole,
pregabalin (Grade A)

CBT indicates cognitive-behavioral therapy; FDA, US Food and Drug Administration; FIQ, Fibromyalgia Impact Questionnaire; SNRI, serotonin and
norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.
Sources: Burckhardt CS, et al. American Pain Society; 2005. Goldenberg DL, et al. JAMA. 2004;292(19):2388-2395. Carville SF, et al. Ann Rheum
Dis. 2008;67(4):536-541. Lyrica prescribing information.

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 Contemporary Management Strategies for Fibromyalgia

appear that any of these agents will be submitted
to the FDA for consideration of approval.
The European League Against Rheumatism
(EULAR) developed guidelines for FM manage-
ment based on best evidence and expert opin-
ion (Table 3).37 A panel of 19 FM experts from
11 European countries performed a systematic
literature review of 146 clinical trials published
from 2002 through 2005 that used ACR diagnos-
tic criteria for FM and focused on FM manage-
ment.37 The panel made 10 recommendations
for FM management including 2 general recom-
mendations, 4 on pharmacologic treatments, and
4 on nonpharmacologic treatments; a multidisci-
plinary treatment approach was emphasized. The
panel found strong evidence for antidepressants
to decrease pain and improve function, specify-
ing milnacipran, duloxetine, amitriptyline, flu-
oxetine, moclobemide, and pirlindole. They
found strong evidence for pain management with
tramadol, pregabalin, tropisetron, and pramipex-
ole, and also recommended considering simple
analgesics (paracetamol [acetaminophen]) and
weak opioids.37 Several nonpharmacologic treat-
ments were also recommended. Weaknesses of the
EULAR guidelines are similar to those of the APS
guidelines and include research evidence and ap-
provals since the publication that render some of
the information obsolete.
The Outcome Measures in Rheumatology Clin-
ical Trials (OMERACT) FM workshop, a group of
21 international research and clinical experts, pub-
lished a consensus statement that made important
advances in prioritizing core symptom domains
by including patient perspectives (Table 4).10
The FM workshops at OMERACT 7 in 2004 and
OMERACT 8 in 2006 were organized to develop a
consensus identifying and prioritizing key FM symp-
toms as “core domains” and to validate and stan-
dardize outcome measures for clinical trials of FM
therapies.10 In addition to well-established criteria
such as pain, fatigue, and sleep quality, OMERACT
added as essential evaluation criteria patient global,
multidimensional function, health-related QOL,
dyscognition, and stiffness.10 OMERACT also em-
phasized the value of composite response (patient
improvement in >2 parameters simultaneously) as
an outcomes measure. The consensus statement
noted, “The ability to ensure clinically meaningful
change in multiple dimensions of fibromyalgia uti-
lizing a composite responder index is desirable.”10
When the OMERACT consensus statement was
published, most clinical trials of most drugs used for
FM had not included composite response. The piv-
otal trials of milnacipran have included composite
outcomes measures, and the roundtable participants
hoped that composite response will be included in
future FM research as specified by OMERACT.

n Table 4. OMERACT Addressed the Multiple Dimensions

of Fibromyalgia
Portion of Respondents Rating
Key Evaluation Criterion Criterion as “Essential,” %
Pain 100
Fatigue 94
Patient global 94
Multidimensional function 86
Tenderness 74
Sleep 66
Health-related quality of life 65
Dyscognition 61
Stiffness 60

OMERACT indicates Outcome Measures in Rheumatology Clinical Trials.

Adapted from Mease P, et al. J Rheumatol. 2007;34(6):1415-1425.

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Reports
 M Guidelines and Current Knowledge About
F als, so the pharmacologic treatments discussed
Pharmacotherapies
Many experts, including the AJMC roundtable
participants, consider the current FM guidelines to
have limited utility for practicing clinicians and
payers. One important reason is that the guidelines
do not reflect the FDA approvals of 3 agents for
FM. The guidelines preceded the FDA approv-
n Table 5. FDA-Approved Agents for Fibromyalgia (FM)
Lyrica41
(Pregabalin)
Date of FDA approval Initial: 2004 (as an anticonvulsant)
For FM: June 2007
Mechanism of action Alpha2 delta ligand
Indications Neuropathic pain associated with
diabetic peripheral neuropathy,
postherpetic neuralgia, adjunctive
therapy for partial-onset seizures,
FM
Studies that established One 14-wk randomized, double-
efficacy for FM blind, placebo-controlled trial, one
6-mo randomized withdrawal study
Primary end points/ Pain reduction (VAS); improve-
outcomes measured ments in patient global (PGIC) and
function (FIQ)
in FM pivotal trials
Recommended dose for FM 150-225 mg bid
75 mg bid
May increase to 150 mg bid
within 1 wk
Maximum dose 225 mg bid
Warnings and precautions Angioedema, hypersensitivity
reactions, peripheral edema
Most common adverse Dizziness, somnolence, dry mouth,
reactions edema, blurred vision, weight
gain, difficulty with concentration/
attention
Scheduling and dependence Schedule V controlled substance;
rapid discontinuation associated
with withdrawal symptoms
FDA indicates US Food and Drug Administration; FIQ, Fibromyalgia Impact Questionnaire; PGIC, Patient Global Impression of Change; SF-36
PCS, Short Form-36 Physical Composite Score; SNRI, serotonin and norepinephrine reuptake inhibitor; VAS, visual analog scale.
S210   n  www.ajmc.com  n JUNE 2009
were by necessity off-label (including those that
later received approval). Many drugs are used for
the control of different FM symptoms, including
SNRIs, anticonvulsants, tricyclic antidepressants
(TCAs), muscle relaxants, SSRIs, opioids, non-
steroidal anti-inflammatory drugs (NSAIDs), and
cyclo-oxygenase (COX)-2 inhibitors.9,19,38 How-
Cymbalta40 Savella39
(Duloxetine Hydrochloride) (Milnacipran Hydrochloride)
Initial: 2004 (as an antidepressant) January 2009 (indicated only for
For FM: June 2008 FM)
SNRI SNRI
Major depressive disorder, gen- FM
eralized anxiety disorder, diabetic
peripheral neuropathic pain, FM
Two randomized, double-blind, Two randomized, double-blind,
placebo-controlled trials (3 mo placebo-controlled trials (6 mo
and 6 mo), 1 randomized, double- and 3 mo)
blind, dose-comparison trial
Pain reduction, improvements in Composite end point of pain
patient global (PGIC) and function reduction (VAS) and improvement
(FIQ) in patient global (PGIC). Also com-
posite end point of pain (VAS),
physical function (SF-36 PCS), and
patient global (PGIC)
60 mg/d 50 mg bid (start 12.5 mg/d,
increase on day 2 to 12.5 mg bid,
Start 30 mg/d for 1 wk, increase on day 4 to 25 mg bid, after day 7
to 60 mg/d to 50 mg bid)
Maximum dose 200 mg/d
Suicidality in children, adoles- Suicidality in children, adolescents,
cents and young adults (all and young adults (all antidepres-
antidepressants); hepatotoxicity, sants); serotonin syndrome,
orthostatic hypotension, sero- elevated blood pressure and heart
tonin syndrome (or neuroleptic rate, seizures, hepatotoxicity,
malignant syndrome), bleeding, bleeding, hyponatremia, activation
hypomania, seizures, urinary of mania, dysuria, narrow angle
retention, hyponatremia, altera- glaucoma, use with alcohol
tions in blood pressure and blood
glucose levels. Interactions with
inhibitors of CYP1A2, CYP2D6
Nausea, dry mouth, constipa- Nausea, headache, constipation,
tion, somnolence, hyperhidrosis, dizziness, insomnia, hot flush,
decreased appetite hyperhidrosis, vomiting, palpita-
tions, heart rate increase, dry
mouth, hypertension
Unscheduled; withdrawal symp- Unscheduled; withdrawal symp-
toms on abrupt discontinuation toms on abrupt discontinuation

ever, only 3 agents have received FDA approval for
this indication: Savella (milnacipran),39 Cymbalta
(duloxetine),40 and Lyrica (pregabalin)41 (Table 5).
FDA approval implies a level of scrutiny and sup-
porting basic research and clinical trial evidence
that is lacking for off-label uses of drugs. In the case
of the FDA-approved FM drugs, the clinical trials
supporting the duloxetine and pregabalin approvals
had single–end-point outcomes measures, whereas
the primary end points for milnacipran trials were
composite measures, a more comprehensive measure
of simultaneous efficacy across multiple symptoms
versus placebo. Since the current FM management
guidelines predate the FDA approvals, they are not
mentioned in the recommendations.
Dr. Dunn (Managed Care): When we see [fibro-
myalgia] patients, they are on generic SSRIs,
generic muscle relaxants, generic antidepres-
sants, and opioids. What drives pharmacy
costs are [long-acting] opioids, which are
known to be generally ineffective.
The FDA-approved drugs for FM belong to
classes that have demonstrated efficacy for FM
management. Pregabalin is an anticonvulsant, and
randomized controlled trials have also supported
the efficacy of another anticonvulsant, gabapen-
tin.16,41 Milnacipran and duloxetine are SNRIs with
demonstrated efficacy and safety in FM; their sero-
tonin- and norepinephrine-reuptake inhibiting ac-
tions may correct functional deficits in descending
pathway pain processing.7,9,39,40 However, 2 other
SNRIs, venlafaxine and desvenlafaxine, have not
had efficacy for FM established in clinical trials.9,42
Some off-label drugs are discussed or recommended
in the guidelines,2,20,37 but many drugs prescribed
off-label for FM may have limited utility for this
purpose. Clinical trial evidence for their efficacy
and safety in FM is limited or absent. Studies have
failed to confirm the efficacy of NSAIDs and COX-
2s in FM.13 Short-term studies have demonstrated
some efficacy with tricyclics, but safety and toler-
ability concerns have limited their use.9,19 Efficacy
in FM clinical trials has not been demonstrated
with opioids, which also carry the potential for de-
pendence and abuse as well as exacerbating pain as
opioid hyperalgesia.9,13 Only a few controlled trials
have been conducted using muscle relaxants for
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Contemporary Management Strategies for Fibromyalgia
FM patients, with mixed results.13 Tramadol, which
combines some opioid activity with SNRI activ-
ity, may have some efficacy, but bears the risk of
withdrawal symptoms, abuse, and serotonin syn-
drome.7,9,12,43 Studies of SSRIs have shown efficacy
for mood and fatigue in FM, but limited efficacy for
pain.13 To be optimally useful, guidelines for FM
management should consider the FDA approvals,
clinical studies of drugs approved for FM, and the
latest evidence regarding all agents used commonly
on- and off-label.
The current guidelines also do not reflect up-
dated analyses of FM treatments. Two recent sys-
tematic reviews, which were completed after the
current guidelines, add substantially to the evidence
base and scientific understanding of FM therapy.
Nishishinya et al systematically reviewed 10 ran-
domized, placebo-controlled trials of amitriptyline
for FM.44 Although amitriptyline 25 mg/day was
associated with significant improvements in some
symptoms, amitriptyline 50 mg did not perform sig-
nificantly better than placebo.44 Of the 10 studies,
8 had durations of only 8 weeks,44 and the 8-week
efficacy shown for amitriptyline 25 mg was not ob-
served at 12 weeks in the study of that length.44 The
10 studies did not report adverse events consistently
and rigorously.44 The authors concluded that no evi-
dence supports the efficacy of amitriptyline at doses
higher than 25 mg/day or for longer than 8 weeks.44
Dr. Flood (Rheumatology): We have no data
about the safety of any of the [older] nonap-
proved drugs in FM patients. Whereas for the
approved agents, the FDA requires trials to
report safety data, and the FDA is watching
out to make sure that the safety data are rel-
evant and honest.
Häuser et al performed a meta-analysis of 18 ran-
domized, placebo-controlled trials of antidepres-
sants used for FM, including TCAs, SSRIs, SNRIs,
and monoamine oxidase inhibitors.25 The authors
found strong evidence for efficacy of some of the
agents, but noted patient preferences and comor-
bidities related to potential adverse effects of these
drugs should be considered before initiating treat-
ment.25 The meta-analysis had several limitations.
It could not compare classes or individual drugs
because of the different combinations of medica-
Reports
tions allowed in each study. Most studies were only
8 weeks in duration. A disparity in sample sizes be-
tween drug classes (eg, small “n” in TCA trials and
large “n” in SNRI trials) could affect the rigor of
observed effect sizes. Not included were the phase
3 pivotal trials of milnaci-pran, outcomes assess-
ment of composite response or physical function,
or discussion of attributes of medications that may
affect compliance, such as tolerability and the po-
tential for drug–drug interactions.
Dr. Goldenberg (Rheumatology): I think I use guide-
lines and most people use guidelines to help
with our gestalt about what is an appropriate
individual therapy. Of course, the limitations
with guidelines in rheumatoid arthritis or in FM
are that it’s such an individual condition. So we
as clinicians have to be aware of the fact that
it just gives us another way to think about the
condition.
The current guidelines for FM management pre-
date these 2 analyses, which would appear to weak-
en the case for some off-label drugs recommended
in the guidelines.
Dr. Beltran (Managed Care): In our organization
clinical guidelines never replace physicians’
clinical judgment and experience…and ulti-
mately when the guideline doesn’t fit the
patient, we defer to the physician’s clinical
judgment and expertise.
Challenges for FM Guidelines
The AJMC roundtable participants observed
that the current FM guidelines are not commonly
used by physicians or payers to make treatment or
formulary decisions. Some physicians, especially
PCPs, find it difficult to keep current with the latest
guidelines for the many disorders they treat and are
not familiar with the guidelines for FM. Guidelines
in general can sometimes be too restrictive to ap-
ply to the unique needs of individual patients with
any disorder, and individualization is crucial in FM
treatment. Participants noted that clinicians should
fit guidelines to the patient, not the patient to the
guidelines. Especially if guidelines are followed rig-
idly in formulary positions, they can be too restric-
tive to individualize patient care and treat patients
early and effectively.
S212   n  www.ajmc.com  n JUNE 2009
In further discussion, the roundtable partici-
pants concluded that the current FM guidelines
have limited practical utility. They lack a straight-
forward recommended treatment algorithm (al-
though an algorithm could be difficult because each
FM patient has a unique set of symptoms and re-
quires individualized treatment). More important,
the usefulness of the latest published guidelines has
been limited by the rapid change in the research
and clinical fields of FM. The guidelines precede or
do not consider recent FDA approvals of 3 agents
for FM or their pivotal trials, and some guidelines
may overemphasize TCAs. The guidelines do not
include evidence from the latest systematic review
analyses. The outcomes measurements in trials
cited for the APS and EULAR guidelines do not
include evaluation criteria deemed essential by
patients and physician experts, as recommended
by OMERACT. Participants observed that guide-
lines can be “double-edged swords,” used not only
to encourage the use of certain treatments but to
justify discouraging other treatments that may be
helpful for individual patients. In the case of FM,
physicians may be forced to use unapproved drugs
off-label before trying FDA-approved drugs. For
lack of guidelines that reflect the latest findings,
clinicians, managed care organizations, and oth-
er stakeholders have diverse understandings and
views on best practices for the treatment of FM.
Clinician prescribing practices vary widely, and
managed care does not have disease management
initiatives in place for FM patients.
Dr. Draud (Psychiatry): When you see real people
who have real disease, patients’ symptoms
don’t always match the treatment guidelines. I
think it’s helpful to have them [guidelines], but
I treat symptoms, not rigid diagnostic criteria
and guidelines.
Updated guidelines for the diagnosis and man-
agement of FM should reflect the rapidly changing
landscape of scientific understanding and advanc-
es in disease management. They should enhance
clinician education as well as clinical practice, be-
cause they could further legitimize FM and clarify
understanding of the disease process. Health plans
could help advance this medical education by dis-

seminating new guidelines to clinicians. Updated
guidelines could also encourage the easing of cur-
rent formulary restrictions on access to effective
FM treatments. The current FM guidelines are
rarely used in formulary development processes;
however, more useful guidelines would be wel-
come. The new guidelines should be geared to-
ward optimizing the 3 critical outcome domains of
FM: clinical, economic, and QOL.
Dr. Flood (Rheumatology): I think in terms of how
you develop guidelines and treatment deci-
sions, we are just at the dawn of a new era in
American medicine. The president has placed
in the stimulus bill billions of dollars to do
comparative effectiveness studies. Those are
some of the areas that researchers need to
latch on to, so we can question whether there
is a difference between amitriptyline and a dif-
ferent drug, and whether there are variabilities
based on patient characteristics. These are
doable trials; we just need the researchers to
have the opportunity and the funds to do it.
Those funds are available as they have never
been before.
To underpin and strengthen new guidelines, more
comparative clinical trials are needed to evaluate the
efficacy and safety of drug therapies for FM. Already
available to include are the FDA-approved agents
and their supporting pivotal trials, which should be
given due consideration in updated guidelines. Also
available are the recent meta-analyses discussed
above, which clarify the evidence to date regarding
some agents. Additional new head-to-head stud-
ies would offer valuable evidence and help resolve
controversies over conflicting data. New trials and
new guidelines should consider patient perspectives
(eg, by using OMERACT criteria and composite
response outcome measures). Guidelines should
recognize early diagnosis and appropriate treatment,
thereby preventing further functional deterioration,
preserving QOL, and realizing cost savings.
Guidelines should be used as a tool for optimal
patient care, which for FM means individualiza-
tion of treatment. Often treatment individualiza-
tion can be best achieved through a collaborative
multidisciplinary team, which might include a
PCP, rheumatologist, pain specialist, psychiatrist,
physical therapist, and/or others. Listening to the
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Contemporary Management Strategies for Fibromyalgia
patient’s concerns and giving council regarding
how to have a better QOL with a chronic illness is
important for optimal outcomes and can be facili-
tated by the additional healthcare encounters that
occur with team treatment. If the patient does not
fit guidelines, the team can defer to clinical judg-
ment and experience. Even when treating patients
with FM without a collaborative team, clinicians
should be able to assess its progression on the dis-
ease continuum and refer to guidelines accord-
ingly. Managed care could develop formularies
and initiate chronic-care disease management
programs that reference guidelines, the latest evi-
dence in the literature, and a consensus of various
specialists while allowing flexibility for patient
individualization
Summary
The current guidelines have been and are a good
attempt to increase awareness of FM, add legitimacy
to the disease state, and outline possible treatment
options. However, they have several limitations,
including the omission of new treatments and re-
cent evidence. Updated or revised guidelines that
include some of the most recent data and informa-
tion could become an important tool to aid in the
successful management of FM.
SECTION 3. CATEGORY MANAGEMENT
OF FM AGENTS: IMPLICATIONS FOR
PATIENT OUTCOMES AND UTILIZATION
MANAGEMENT
Summary of Roundtable Discussions of Issues
and Needs Relating to FM
The AJMC roundtable participants agreed
that due to the prevalence, patient burden, and
costs, all FM patients should be diagnosed and
managed appropriately. They also agreed that
an opportunity to educate providers about FM
diagnosis and management exists; such educa-
tion could improve patient outcomes and lower
costs. The participants noted that physicians
have several choices at their disposal to treat FM,
including 3 FDA-approved agents, along with
nonpharmacologic treatments and some off-label
medications. They found current guidelines to
be a reasonable attempt to identify appropriate
treatments, but noted the guidelines are outdated,
Reports
not widely used by plans or providers, and have
limitations. Participants agreed the best manage-
ment approach for FM would allow patients open
access to all available treatments, with individu-
alized treatment decisions made jointly between
the physician and patient. Participants noted that
current access to FDA-approved agents to treat
FM is often restricted, allowed only after failure
of treatment with other agents (typically generic
drugs), for which FM is an off-label use. This is
a common practice for many medical conditions,
including FM, in managed care environments.
Discussion then turned to establishment of an FM
category on payer formularies as a step toward le-
gitimizing the disease state and educating provid-
ers about FDA-approved and non–FDA-approved
treatments.
Dr. Lee (Internal Medicine): With new medica-
tions, it’s very difficult to get approval [insur-
ance coverage]. There is a lot of paperwork, a
lot of step therapy, and it gets the physician
and patient frustrated. When they don’t get
approved, they will often just give up.
Formulary Categories and Access to Treatment
A specific therapeutic category for FM with-
in payer formularies does not exist within most
formularies today. This, along with a lack of di-
agnosis coding on prescription claims, makes it
difficult for health plans to track the prevalence of
the disease. This inability to track FM may have
helped perpetuate a scant awareness of the disease
in managed care and inattention to it in chronic
disease management plans, educational programs,
and other initiatives. Lack of a category for FM
also means that the drugs used (off-label) for FM
are found in other categories based on their ap-
proved indications. Even 2 of the FDA-approved
drugs for FM are classified in 1 or more other cat-
egories based on their approvals for other condi-
tions, which often are their primary indication.
Duloxetine may be found under depression and/
or pain management. Pregabalin may be listed
under anticonvulsants and/or pain management.
Milnacipran, however, is the first drug with FDA
approval for FM only, and no roundtable partici-
pant was aware of any formulary with a category
for FM.
S214   n  www.ajmc.com  n JUNE 2009
Category requirements of the United States
Pharmacopeia (USP) may influence Medicare Part
D formulary development in ensuring that drugs
in the categories are included. The USP currently
lists duloxetine and pregabalin under their primary
therapeutic category only (duloxetine under an-
tidepressants, pregabalin under anticonvulsants).
The USP formulary has been updated annually,
but in agreement with the Centers for Medicare
& Medicaid Services (CMS), USP is going to a
3-year update cycle, leaving milnaci-pran cur-
rently without a category. Medicare Part D health
plans are not required to follow the USP model
formulary for categorization, but they are measured
against it. As for commercial formularies, health
plans frequently keep their commercial and Medi-
care formularies consistent, but the plans are free
to impose limitations or restrictions. Thus USP re-
quirements may have had an indirect influence on
the development of formularies that do not include
the FDA-approved treatments in an FM category.
The lack of a category for FM may indirectly
affect patient access to appropriate treatments,
including treatments indicated by the FDA. For-
mularies commonly control access to the FDA-
approved drugs for FM; duloxetine and pregabalin
use is restricted on approximately half of commer-
cial health plans.
Ms. Brown (Patient Advocacy): What a lot of these
barriers do…is further delay the appropriate
care and management of these patients…
making the condition far worse. So, what we
need to do is get to early intervention through
recognition and care that’s appropriate and
that doesn’t have other burdens from access
to care as well as the willingness to pay for
that care.
Problems with access to treatment contribute
to FM patients’ dissatisfaction with their health-
care. A national patient survey conducted by
the APF and National Fibromyalgia Association
(NFA) demonstrated widespread insurance or
managed care problems.45 Common difficulties
included incomplete coverage for pain treatment
options, delays in preauthorization and access to
FDA-approved medications, prolonged appeals
processes, and repetitive denials of coverage.45

Some of these problems might be related to the
lack of an FM category on formularies. Without
a category for FM, health plans may not have a
unique, comprehensible FM treatment paradigm
that clearly identifies FDA-approved therapies.
Dr. Jain (Psychiatry): Legitimacy is what this dis-
order is begging for. Anything that can add to
the legitimacy will serve everyone’s interest
here. I look at formularies as one more layer
of protection for me, because I know they are
watching out or reading the picture at a level
that I’m not, maybe. I actually like the fact that if
your plan says FM is the category and this drug
is approved, I know they have looked at it. I like
that. I know clinicians and primary physicians
like it too.
Often patients tell their physicians about their
drug coverage policies, which can guide prescribing
practices. FM patients looking at formularies may
not see a drug they can associate with their disease.
Lack of a category for FM might lead physicians and
patients to look at categories like pain management
and possibly choose less appropriate treatments,
such as opiates. Physicians can select any drug,
but many have limited education on FM or the 3
FDA-approved agents. Thus the lack of a category
may leave patients as well as their PCPs without
guidance from the health plan for appropriate FM
management.
 ategorizing FM on Formularies to Benefit
C with the inquiry.
Patients, Clinicians, and Payers
Most importantly, the roundtable participants
felt that a new category for FM on payer formu-
laries could help legitimize the FM disease state.
Patients and physicians would be able to see the
disease listed in the formulary rather than having
to search through “similar” categories for some-
thing that may apply to the situation. Greater le-
gitimacy for FM would encourage more research
interest, better public awareness, less stigma for pa-
tients, and possibly more government funding for
research. Greater legitimacy could therefore fur-
ther the advancement of medical progress against
this chronic, debilitating disease.
A new category would also raise awareness
of FM as a diagnosis to consider. It would help
VOL. 15, No. 7 n  The American Journal of Managed Care  n S215
Contemporary Management Strategies for Fibromyalgia
health plans recognize the diagnosis and autho-
rize appropriate treatment. It would also encour-
age action by clinicians who hesitate to diagnose
or treat due to confusion or misunderstanding
about the disease. A new category would support
the need for intervention in FM, thereby perhaps
helping reduce the time and effort wasted on in-
accurate diagnoses.
A new FM category would serve as part of a
broader initiative to educate the medical com-
munity and patients about the FM disease state.
The category would support the need for better
education identified in Section 1 of this supple-
ment. Better education, in turn, can lead to bet-
ter outcomes. A new category would offer FM
patients the validation and reassurance they need
while helping them learn about their disease.
A new category would educate providers about
FM and help separate clinicians’ thinking about
treating FM from their thinking about treating
pain alone, depression, anxiety, or an unknown
diagnosis.
Ms. Brown (Patient Advocacy): If [milnacipran]
goes to its own category, it’s an opportunity
for the patient advocacy groups to design
outreach information to our constituents to
help them be better informed and how to ask
the right questions. Not only would they say,
“I saw this in a magazine, can I take this?”
They can also look and determine whether it
is available through their insurance company.
If it isn’t, they can ask why not and continue
A new category would further educate patients
and physicians about the drug options available for
FM. Options presented under the category in com-
mercial plan formularies would include the 3 FDA-
approved agents. (Other agents, such as TCAs,
could be listed with notations that they do not have
FDA approval.) Listing the FDA approvals within
the FM category would encourage appropriate on-
label utilization. In particular, appropriate catego-
rization of milnacipran, which is indicated only for
FM, would encourage approved on-label utilization
and discourage the off-label prescribing that could
occur if it were classified in a non-FM category.
A category for FM would contribute to im-
proved management of FM drugs by payers, as
Reports
it provides an opportunity to list and delineate
agents with proven efficacy and effectiveness.
Dr. Lee (Internal Medicine): The thing is educa-
tion. Knowing that there is a category for
any condition, let alone FM, stimulates the
decision to look into the options and the evi-
dence behind it. For the patient, it’s actually
good, because we can then tell them what the
efficacy is. I think this is a way to open up a
dialogue.
Although identification of FM by phar-
macy data alone is problematic, use of that in-
formation combined with medical utilization
data can more accurately identify FM patients
and provide a platform for outcomes research.
With this form of integrated data, assessment
of cost-effectiveness becomes a reality and puts
payers in position to better guide benefit cov-
erage for FM treatment and disease manage-
ment plans. This could lead to greater patient
access to the most effective treatments and
still enable health plans to manage utilization.
Implementation of a new FM category would vary
by organization, and the process to create such a
class or category for FM may include:
• A literature review to establish an evidence
base of efficacy and safety data
• Discussion with plan clinicians, including con-
sultation with expert specialists in different
areas (pain, rheumatology, neurology, etc)
Dr. Dunn (Managed Care): I think the way it could
be used is more of an educational approach,
which would be the purpose of having a
category.
Dr. Goldenberg (Rheumatology): A responsibility
for managed care is determining the most
cost-effective care for your clients. And I think
we have shown you that making a diagnosis
of FM is very important in cost-effectiveness.
It saves patients, doctors, and the government
money. We know that for sure. There is a lot
of data, and categorization might help you
with that.
S216   n  www.ajmc.com  n JUNE 2009
• Consideration of FDA approvals, govern-
ment guidelines and advisories, and guide-
lines/statements from medical organizations
• Inclusion of unapproved drugs with effec-
tiveness evidence for FM, but with annota-
tions to their lack of FDA approval
• Cost considerations or cost/benefit analyses
for individual drugs to be listed in the
formulary.
Dr. Bitton (Managed Care): Guidelines are used in
the review of new products; and when those
products come up for review annually, we
will take into consideration changes to those
guidelines, as well as discussions from the
community, physicians, and from among fel-
low pharmacists.
Dr. Draud (Psychiatry): There has been attention
with regard to cost versus care versus patient.
The fact is we are on the same team, and there
shouldn’t be this tension against managed
care. The bottom line is the patient is supposed
to be our primary focus. If, in fact, we raise
the level of awareness and education and help
everybody get on the same page, costs will go
down if we treat the illness earlier.
Summary
The AJMC roundtable participants agreed
that a separate category for FM in drug formular-
ies would further legitimize FM as a unique con-
dition and support education for the medical and
patient communities. With this step forward, all
key stakeholders, including physicians, payers,
and patient advocates, can work collaboratively
on behalf of their patients to facilitate earlier ac-
curate diagnosis and more appropriate treatment,
including improved patient access to the most ef-
fective treatments. Accurate diagnosis and safe,
effective treatment will satisfy the 3 critical out-
comes that frame the unique challenge of FM:
• Clinical: alleviating symptoms and improv-
ing patients’ physical function
• Economic: reducing the high direct and in-
direct costs associated with FM

• Quality of life: preventing disability and
maintaining employment and social in-
volvement, thereby improving QOL.
Dr. Flood (Rheumatology): I think this is a crucial
time in the history of FM and its diagnosis and
management. I think and I hope that some
of the data that we have covered today will
help people understand that if we treat people
early, if we diagnose them accurately, then
we can save the healthcare system, and we
can save patients a lot of money and a lot of
suffering.
Participant Affiliations: From the Department of Pain
Medicine, Associate Professor, Clinical Anesthesiology,
Stony Brook School of Medicine, Stony Brook University
Hospital, Stony Brook, NY (CWA); Outpatient Services,
Monarch Healthcare, Irvine, CA (RB); Pharmacy Services,
Health Plan of Nevada/Sierra Health & Life, Las Vegas,
NV (RKB); Communications Department, American Pain
Foundation, Smithsburg, MD (MAB); Forest Research
Institute, Jersey City, NJ (RD, ID); Medical Director of
Psychiatry and Addiction Medicine, Baptist Hospital
and Middle Tennessee Medical Center, Nashville, TN
(JWD); SelectHealth, Inc, Salt Lake City, UT (JDD);
Musculoskeletal Medical Specialists, The Ohio State
University College of Medicine and Public Health,
Columbus, OH (JF); Family Medicine, Ashville, OH
(DF); Johns Hopkins HealthCare, LLC, Glen Burnie, MD
(HG); National Fibromyalgia Association, Anaheim, CA
(RMG); Department of Rheumatology, Newton-Wellesley
Hospital, and Professor of Medicine, Tufts University
School of Medicine, Newton, MA (DLG); Adult and
Psycho-Pharmacology Research, R/D Clinical Research,
Inc, Lake Jackson, TX (RJ); Internal Medicine, Asheboro,
NC (KL); and Navarro Pharma, LLC, Green Cove Springs,
FL (RPN).
Funding Source: This supplement was supported by
Forest Laboratories, Inc., New York, NY, and Cypress
Bioscience, Inc., San Diego, CA, USA.
Participant Disclosures: The authors (CWA, RB,
RKB, MAB, JWD, JDD, JF, DF, HG, RMG, DLG, RJ, KL,
RPN) were members of the paid advisory board for Forest
and received payment for involvement in the prepara-
tion of this manuscript; an employee of Forest Research
Institute (RD, ID) and owner of Forest Laboratories stock
(RD); consultant/paid advisory board member (DLG, RJ),
received honoraria (DLG, RJ), and attended meetings/
conferences (DLG, RJ) for Forest, Pfizer, and Lilly, and
received lecture fees (DLG) from Pfizer; attended meet-
ings/conferences for Lilly (RJ), and board member for Lilly,
Forest, and Pfizer (RJ).
Participant Information: Concept and design (CWA,
RB, RKB, RD, JWD, JF, DF, RJ, KL); acquisition of data
(MAB, JWD, JDD, DLG); analysis and interpretation of
data (RD, JWD, JDD, JF, DF, HG, DLG, KL); drafting of
the manuscript (CWA, RB, RKB, MAB, JWD, HG, RMG,
DLG, RJ, KL); critical revision of the manuscript for impor-
tant intellectual content (CWA, RB, RKB, MAB, JWD,
DF, RD, ID, JDD, JF, HG, RMG, DLG, RJ, KL, RPN); and
helped supply resources for this supplement (RMG).
VOL. 15, No. 7 n  The American Journal of Managed Care  n S217
Contemporary Management Strategies for Fibromyalgia
Address correspondence to: Robert P. Navarro,
PharmD, Navarro Pharma, LLC, 411 Walnut St, #4641,
Green Cove Springs, FL 32043. E-mail: Robert.p.navarro@
gmail.com.
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